Simvastatin is an oral therapy being studied as a potential treatment to slow the progression of secondary progressive multiple sclerosis (SPMS).
The compound belongs to a group of drugs called statins, which are widely approved to lower cholesterol levels and reduce the risk of cardiovascular problems. Statins, however, also reduce inflammation and are thought to promote recovery and regeneration of nerve cells, which makes them appealing candidates for treating MS.
Simvastatin was initially marketed by Merck under the brand name Zocor. Generic versions became available in most countries after the patent expired.
Multiple sclerosis (MS) is caused by the immune system mistakenly targeting myelin, a protective layer surrounding nerve fibers, in the brain and spinal cord. This results in inflammation and progressive nerve cell damage, leading to a range of neurological symptoms.
Statins are a group of small molecules that, in addition to their cholesterol-lowering properties, seem to have anti-inflammatory and neuroprotective effects.
Exactly how these treatments alter the immune system is not clearly understood. But statins have been shown to interfere with pro-inflammatory immune cells involved in MS inflammation — including T-cells and microglia — prompting them to acquire an anti-inflammatory role. This results in lower levels of pro-inflammatory molecules and an increase in anti-inflammatory ones.
Statins also can block the production of adhesion molecules in blood vessel cells, which ultimately prevents the migration of immune cells through the blood-brain barrier, a semi-permeable membrane that regulates which molecules and cells in circulation are able to enter the brain and spinal cord.
These molecules are believed to reduce nerve cell excitability and lower the amount of reactive oxygen species, which also are key contributors to neuronal damage in neurodegenerative conditions like MS.
The medicine is available in film-coated tablets taken orally. The maximum recommended dose for its approved indications is 40 mg, once daily, but MS clinical trials are mostly testing simvastatin at a daily dose of 80 mg.
An initial clinical study investigated simvastatin in 30 patients with early relapsing-remitting MS (RRMS). All had evidence of brain lesions with active inflammation on MRI scans and received 80 mg of the medication, once daily for six months. Results showed that the number and volume of brain lesions were significantly reduced, by more than 40%, after six months on simvastatin.
Subsequent trials tested simvastatin as an add-on therapy to Biogen’s Avonex, an interferon-based therapy approved for relapsing forms of MS.
A Phase 3 trial (NCT00668343) sponsored by the Tehran University of Medical Sciences, enrolled 85 RRMS patients who had been on Avonex for at least three months. Participants received a 40 mg dose of simvastatin, or a placebo, while continuing their standard treatment.
After one year, the combination of simvastatin and Avonex was found to significantly reduce the number of relapses experienced by patients. While other outcomes, such as disability progression and the number of brain lesions, also tended to improve with simvastatin, those results failed to reach statistical significance.
Biogen sponsored a similar Phase 4 trial (NCT00492765), called SIMCOMBIN, that also yielded conflicting results. That study had enrolled more than 300 RRMS patients, who received Avonex in the first three months, and then were then randomly assigned to additional treatment with 80 mg of simvastatin or a placebo for up to three years.
The trial failed to meet its primary goal of reduced relapse rates. In fact, patients on simvastatin showed a greater number of relapses per year than those on a placebo, although the results did not reach statistical significance. The proportion of patients with sustained disability progression also was not significantly different between the two groups. Nor was there a significant difference in the number of new or enlarging brain lesions.
Researchers at the Imperial College London, in the U.K., conducted the MS-STAT Phase 2 trial (NCT00647348) to determine if simvastatin could reduce the loss of brain volume in people with SPMS. The trial enrolled 140 patients whose major cause of disability worsening in the prior two years was a steady progression, although patients could still be experiencing occasional relapses.
Participants were randomly assigned to receive simvastatin or a placebo, once daily for two years. Those on the active medication received 80 mg daily, but were first given a 40 mg dose over one month before increasing to the full dosage.
Simvastatin treatment resulted in a significant, 43% lower loss of brain volume per year, compared with a placebo, the results showed. There also were significant reductions in total disability and in the patient-reported physical impact of MS. These benefits were independent of the medicine’s effect on cholesterol levels.
The mean number of relapses per year and the proportion of patients with new or enlarging lesions on MRI scans were not different between the groups. But additional analyses revealed better cognitive and physical function among those on simvastatin.
A Phase 3 trial called MS-STAT2 (NCT03387670), launched in 2018, is investigating simvastatin in a larger population of SPMS patients. Similar to the previous trial, patients still could be experiencing relapses, but their major cause of disability worsening had to be steady progression.
Sponsored by the University College London, the trial enrolled 964 patients and randomly assigned them to take daily simvastatin — 40 mg over the first month and 80 mg thereafter — or a placebo, for three years.
The study’s main goal is to assess the treatment’s impact on sustained disability progression, defined as an increase in Expanded Disability Status Scale (EDSS) scores lasting six months or more. Secondary measures include changes in quality of life, dexterity, vision, fatigue, and walking ability. The number and severity of relapses, and cognitive performance also are secondary measures.
Patient enrollment was complete in December 2021, and top-line data is expected in August 2023.
According to clinical trial data, the most common side effects of simvastatin in MS patients include:
The treatment was generally safe and well-tolerated. Most side effects were mild in severity and occurred at similar frequencies in the simvastatin and placebo groups.
Simvastatin has not been rigorously studied during pregnancy, but research indicates it may cause harm to a developing fetus. Based on its prescribing information for other indications, patients who are pregnant or plan to become pregnant should not take simvastatin. Use of the medication also should be avoided during breastfeeding, as a reduction in cholesterol production may result in severe side effects in nursing infants.
Multiple Sclerosis News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.
Simvastatin is a small molecule currently in clinical trials for the treatment of multiple sclerosis (MS). The compound is widely approved to lower cholesterol levels and protect from cardiovascular diseases. But it also has anti-inflammatory and neuroprotective effects that may help people with MS.
Simvastatin has shown promising results in a Phase 2 trial involving people with secondary progressive multiple sclerosis, which encouraged the launch of a larger Phase 3 trial in this patient population. Positive results from this larger trial may potentially support an application requesting simvastatin’s approval by the U.S. Food and Drug Administration. It still could take several years before the therapy is approved, however.
Clinical trials of simvastatin in multiple sclerosis have not included patients who were pregnant. According to its label for other indications, simvastatin may cause fetal harm and patients should talk with their healthcare team if they become or plan to become pregnant while on treatment.
Some patients in clinical trials started seeing results after about two years of therapy. In a Phase 2 trial involving people with secondary progressive multiple sclerosis, a daily simvastatin dose of 80 mg lowered brain volume loss by 43% and improved measures of disability two years after starting treatment. Whether significant results can be observed in this population at earlier time points remains unknown.
Weight gain and hair loss were not reported as side effects of simvastatin in multiple sclerosis clinical trials. However, some people who received the medication for other indications — it is approved as a cholesterol-lowering therapy — have experienced hair loss. There also are some isolated reports of weight gain in people receiving this medicine. Patients should talk with their healthcare provider if such events occur.
Get regular updates to your inbox.